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Fabrication and transfer of fragile 3D PDMS microstructures
KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).ORCID iD: 0000-0002-0441-6893
KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.ORCID iD: 0000-0001-8531-5607
Show others and affiliations
2012 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 22, no 8, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour.

Place, publisher, year, edition, pages
2012. Vol. 22, no 8, 1-9 p.
Keyword [en]
Microfluidic Devices, Layer
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:kth:diva-95357DOI: 10.1088/0960-1317/22/8/085009ISI: 000306649000009Scopus ID: 2-s2.0-84864447006OAI: oai:DiVA.org:kth-95357DiVA: diva2:527942
Note

QC 20150624

Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Microfluidic blood sample preparation for rapid sepsis diagnostics
Open this publication in new window or tab >>Microfluidic blood sample preparation for rapid sepsis diagnostics
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Sepsis, commonly referred to as blood poisoning, is a serious medical condition characterized by a whole-body inflammatory state caused by microbial infection. Rapid treatment is crucial, however, traditional culture-based diagnostics usually takes 2-5 days.  The overall aim of the thesis is to develop microfluidic based sample preparation strategies, capable of isolating bacteria from whole blood for rapid sepsis diagnostics. 

Although emerging technologies, such as microfluidics and “lab-on-a-chip” (LOC) devices have the potential to spur the development of protocols and affordable instruments, most often sample preparation is performed manually with procedures that involve handling steps prone to introducing artifacts, require skilled technicians and well-equipped, expensive laboratories.  Here, we propose the development of methods for fast and efficient sample preparation that can isolate bacteria from whole blood by using microfluidic techniques with potential to be incorporated in LOC systems.

We have developed two means for high throughput bacteria isolation: size based sorting and selective lysis of blood cells. To process the large blood samples needed in sepsis diagnostics, we introduce novel manufacturing techniques that enable scalable parallelization for increased throughput in miniaturized devices.

The novel manufacturing technique uses a flexible transfer carrier sheet, water-dissolvable release material, poly(vinyl alcohol), and a controlled polymerization inhibitor to enable highly complex polydimethylsiloxane (PDMS) structures containing thin membranes and 3D fluidic networks.

The size based sorting utilizes inertial microfluidics, a novel particles focusing method that operates at extremely high flow rates. Inertial focusing in flow through a single inlet and two outlet, scalable parallel channel devices, was demonstrated with filtration efficiency of >95% and a flowrate of 3.2 mL/min.

Finally, we have developed a novel microfluidic based sample preparation strategy to continuously isolate bacteria from whole blood for downstream analysis. The method takes advantage of the fact that bacteria cells have a rigid cell wall protecting the cell, while blood cells are much more susceptible to chemical lysis. Whole blood is continuously mixed with saponin for primary lysis, followed by osmotic shock in water. We obtained complete lysis of all blood cells, while more than 80% of the bacteria were readily recovered for downstream processing.

Altogether, we have provided new bacteria isolation methods, and improved the manufacturing techniques and microfluidic components that, combined offer the potential for affordable and effective sample preparation for subsequent pathogen identification, all in an automated LOC format.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. ix, 40 p.
Series
Trita-FYS, ISSN 0280-316X ; 2012:39
Keyword
3D fluidic networks, bacteria isolation, inertial microfluidics, lab-on-chip, microfluidics, particle filtration, PDMS membrane, selective cell lysis. sepsis
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-96313 (URN)978-91-7501-428-9 (ISBN)
Presentation
2012-06-15, FD5 (The Svedberg Hall), Albanova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 14:00 (English)
Opponent
Supervisors
Funder
EU, FP7, Seventh Framework Programme
Note
QC 20120611Available from: 2012-06-11 Created: 2012-06-01 Last updated: 2012-06-11Bibliographically approved
2. Polymer microfluidic systems for samplepreparation for bacterial detection
Open this publication in new window or tab >>Polymer microfluidic systems for samplepreparation for bacterial detection
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sepsis, caused by blood stream infection, is a very serious health condition thatrequires immediate treatment using antibiotics to increase the chances for patientsurvival. A high prevalence of antibiotic resistance among infected patients requiresstrong and toxic antibiotics to ensure effective treatment. A rapid diagnostic devicefor detection of antibiotic resistance genes in pathogens in patient blood would enablean early change to accurate and less toxic antibiotics. Although there is a pressingneed for such devices, rapid diagnostic tests for sepsis do not yet exist.In this thesis, novel advances in microfabrication and lab-on-a-chip devices arepresented. The overall goal is to develop microfluidics and lab-on-a-chip systems forrapid sepsis diagnostics. To approach this goal, novel manufacturing techniques formicrofluidics systems and novel lab-on-a-chip devices for sample preparation havebeen developed.Two key problems for analysis of blood stream infection samples are that lowconcentrations of bacteria are typically present in the blood, and that separation ofbacteria from blood cells is difficult. To ensure that a sufficient amount of bacteria isextracted, large sample volumes need to be processed, and bacteria need to be isolatedwith high efficiency. In this thesis, a particle filter based on inertial microfluidicsenabling high processing flow rates and integration with up- and downstream processesis presented.Another important function for diagnostic lab-on-a-chip devices is DNA amplificationusing polymerase chain reaction (PCR). A common source of failure for PCRon-chip is the formation of bubbles during the analysis. In this thesis, a PCR-on-chipsystem with active degassing enabling fast bubble removal through a semipermeablemembrane is presented.Several novel microfabrication methods were developed. Novel fabrication techniquesusing the polymer PDMS that enable manufacturing of complex lab-on-a-chipdevices containing 3D fluidic networks and fragile structures are presented. Also,a mechanism leading to increased accuracy in photopatterning in thiol-enes, whichenables rapid prototyping of microfluidic devices, is described. Finally, a novel flexibleand gas-tight polymer formulation for microfabrication is presented: rubbery OSTE+.Together, the described achievements lead to improved manufacturing methodsand performances of lab-on-a-chip devices, and may facilitate future development ofdiagnostic devices.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2014. xiv, 65 p.
Series
TRITA-EE, ISSN 1653-5146 ; 2014:038
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-151244 (URN)978-91-7595-244-4 (ISBN)
Public defence
2014-10-03, FR4 (Oskar Klein-auditoriet), Roslagstullsbacken 21, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20140916

Available from: 2014-09-17 Created: 2014-09-15 Last updated: 2014-09-19Bibliographically approved
3. From Lab to Chip – and back: Polymer microfluidic systems for sample handling in point-of-care diagnostics
Open this publication in new window or tab >>From Lab to Chip – and back: Polymer microfluidic systems for sample handling in point-of-care diagnostics
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis contributes to the development of Lab-on-a-Chip systems that enables reliable, rapid medical diagnostics at the point-of-care. These contributions are focused on microfluidic Lab-on-a-Chip systems for sepsis diagnosis, autonomous sample-to-answer tests, and dried blood spot sampling.

Sepsis is a serious condition with high mortality and high costs for society and healthcare. To facilitate rapid and effective antibiotic treatment, improved sepsis diagnostics is needed. Diagnosis of sepsis requires the processing of relatively large blood volumes, creating a need for novel and effective techniques for the handling of large volume flows and pressures on chip. Components, materials, and manufacturing methods for pneumatically driven Lab-on-a-Chip systems have therefore been developed in this thesis. Microvalves, an essential component in many Lab-on-a-Chip systems have been the focus on several of the advances: a novel elastomeric material (Rubbery Off-Stoichiometric-Thiol-Ene-Epoxy) with low gas and liquid permeability; the first leak-tight vertical membrane microvalves, allowing large channel cross-sections for high volumetric flow throughput; and novel PDMS manufacturing methods enabling their realization. Additionally, two of the new components developed in this thesis focus on separation of bacteria from blood cells based on differences in particle size, and cell wall composition: inertial microfluidic removal of large particles in multiple parallel microchannels with low aspect ratio; and selective lysis of blood cells while keeping bacteria intact. How these components, materials and methods could be used together to achieve faster sepsis diagnostics is also discussed.

Lab-on-a-Chip tests can not only be used for sepsis, but have implications in many point-of-care tests. Disposable and completely autonomous sampleto- answer tests, like pregnancy tests, are capillary driven. Applying such tests in more demanding applications has traditionally been limited by poor material properties of the paper-based products used. A new porous material, called “Synthetic Microfluidic Paper”, has been developed in this thesis. The Synthetic Microfluidic Paper features well-defined geometries consisting of slanted interlocked micropillars. The material is transparent, has a large surface area, large porous fraction, and results in low variability in capillary flowrates. The fact that Synthetic Microfluidic Paper can be produced with multiple pore sizes in the same sheet enables novel concepts for self-aligned spotting of liquids and well-controlled positioning of functional microbeads.

Diagnostic testing can also be achieved by collecting the sample at the point-of-care while performing the analysis elsewhere. Easy collection of finger-prick blood in paper can be performed by a method called dried blood spots. This thesis investigates how the process of drying affects the homogeneity of dried blood spots, which can explain part of the variability that has been measured in the subsequent analysis. To reduce this variability, a microfluidic sampling chip has been developed in this thesis. The chip, which is capillary driven, autonomously collects a specific volume of plasma from a drop of blood, and dry-stores it in paper. After sampling, the chip can be mailed back to a central lab for analysis.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. xiii, 75 p.
Series
TRITA-EE, ISSN 1653-5146 ; 2016:002
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-180740 (URN)978-91-7595-844-6 (ISBN)
Public defence
2016-02-05, F3, Lindstedtsvägen 26, KTH, Stockholm, 09:00 (English)
Opponent
Supervisors
Note

QC 20160122

Available from: 2016-01-22 Created: 2016-01-22 Last updated: 2016-01-22Bibliographically approved

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Haraldsson, TommyHansson, Jonasvan der Wijngaart, Wouter

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